title: Proposed explanation for S-adenosylhomocysteine hydrolase deficiency in purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase-deficient patients.
abstract: We have examined the basis for the recently reported, but unexplained deficiency of S-adenosylhomocysteine hydrolase (AdoHcyase) in the erythrocytes of patients with genetic deficiencies of purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase. We found that a hemolysate from a patient with purine nucleoside phosphorylase deficiency had only 7% of control AdoHcyase activity, conforming the original observation. Of the purine nucleosides known to accumulate in nucleoside phosphorylase-deficient patients, inosine alone caused the phosphate-dependent, irreversible inactivation of purified human placental AdoHcyase, and of AdoHcyase in intact erythrocytes and cultured lymphoblastoid cells. Hypoxanthine did not inactivate purified AdoHcyase, but potentiated the effect of inosine in intact hypoxanthine-guanine phosphoribosyltransferase-deficient human lymphoblastoid cells. This presumably resulted from the ability of hypoxanthine to shift the equilibrium of the nucleoside phosphorylase reaction, preventing inosine breakdown. This could account for the partial AdoHcyase deficiency reported in hypoxanthine-guanine phosphoribosyltransferase-deficient patients. We have also demonstrated the AdoHycase-catalyzed synthesis of S-inosylhomocysteine from inosine and L-homocysteine, a reaction which may occur in nucleoside phosphorylase-deficient patients.
mesh_terms: D043383:Adenosylhomocysteinase; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors / Q000172:deficiency*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency*; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology; D010430:Pentosyltransferases / Q000172:deficiency*; D010710:Phosphates / Q000378:metabolism; D010920:Placenta / Q000201:enzymology; D011684:Purine Nucleosides / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency*; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000201:enzymology*
chemical_list: D010710:Phosphates; D011684:Purine Nucleosides; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; D007041:Hypoxanthine Phosphoribosyltransferase; D006867:Hydrolases; D043383:Adenosylhomocysteinase